Gene expression profile in functioning and non-functioning nodules of autonomous multinodular goiter from an area of iodine deficiency: unexpected common characteristics between the two entities.

PURPOSE: Toxic multinodular goiter is a heterogeneous disease associated with hyperthyroidism frequently detected in areas with deficient iodine intake, and functioning and non-functioning nodules, characterized by increased proliferation but opposite functional activity, may coexist in the same gland. To understand the distinct molecular pathology of each entity present in the same gland, the gene expression profile was evaluated by using the Affymetrix technology. METHODS: Total RNA was extracted from nodular and healthy tissues of two patients and double-strand cDNA was synthesized. Biotinylated cRNA was obtained and, after chemical fragmentation, was hybridized on U133A and B arrays. Each array was stained and the acquired images were analyzed to obtain the expression levels of the transcripts. Both functioning and non-functioning nodules were compared versus healthy tissue of the corresponding patient. RESULTS: About 16% of genes were modulated in functioning nodules, while in non-functioning nodules only 9% of genes were modulated with respect to the healthy tissue. In functioning nodules of both patients and up-regulation of cyclin D1 and cyclin-dependent kinase inhibitor 1 was observed, suggesting the presence of a possible feedback control of proliferation. Complement components C1s, C7 and C3 were down-regulated in both types of nodules, suggesting a silencing of the innate immune response. Cellular fibronectin precursor was up-regulated in both functioning nodules suggesting a possible increase of endothelial cells. Finally, Frizzled-1 was down-regulated only in functioning nodules, suggesting a role of Wnt signaling pathway in the proliferation and differentiation of these tumors. None of the thyroid-specific gene was deregulated in microarray analysis. CONCLUSION: In conclusion, the main finding from our data is a similar modulation for both kinds of nodules in genes possibly implicated in thyroid growth.

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment.

PURPOSE: Reliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT) are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC). PATIENTS AND METHODS: Fifty-four new patients with nodular goiter were enrolled and analysed together with those previously published by our group for a total of 135 cases. bCT and casCT were measured by a highly sensitive method and the results compared with histological findings. In a subgroup of patients, cardiac rhythm was recorded before and during the calcium test. RESULTS: In both females (F) and males (M), there was a significant correlation between tumor size and bCT levels (P < 0.001). The receiver operating characteristic plot analyses showed that, for bCT, the new cut-off points able to separate non-MTC from MTC patients were > 30 (F) and > 34 pg/mL (M), whereas the best casCT thresholds were > 79 (F) and > 466 pg/mL (M). bCT was shown to harbour a high accuracy, though some cases were diagnosed only upon stimulation test. Importantly, combining bCT, below or above the cut-offs, with casCT above the cut-offs, all the MTC cases were correctly identified. A reversible sinus bradycardia was observed in 9% of cases during the test. CONCLUSIONS: Refined cut-offs for bCT and casCT in patients with nodular goiter are reported. Sensitive bCT was shown to have a high accuracy, but the combination with casCT data was needed to identify all MTC cases. The reliability and safety of calcium test strongly favour the routine use of CT determination in nodular thyroid disease.

Cochlear implantation in patients with Pendred syndrome.

OBJECTIVE: To examine the outcomes of cochlear implantation in children with Pendred Syndrome. MATERIAL AND METHODS: A retrospective case series of nine pediatric patients with Pendred syndrome undergoing cochlear implantation at a tertiary academic medical center from 2003 to 2017. RESULTS: All patients were diagnosed with bilateral mild-to-profound to severe-to-profound sensorineural hearing loss and used hearing aids prior to implantation. Preoperative imaging results revealed that all patients exhibited bilateral enlarged vestibular aqueducts and 8 of 9 had cochlear dysplasia equivalent to Incomplete Partition II. Despite inner ear malformations, all electrodes were successfully implanted with minimal complications and favorable post-operative audiological outcomes. CONCLUSIONS: Cochlear implantation is an effective and successful treatment for severe-to-profound hearing loss in children with Pendred syndrome and for whom traditional amplification aids provide limited benefit. With early intervention, cochlear implantation allows speech and cognitive development in Pendred children comparable to that of normal hearing individuals, allowing patients to learn in a mainstream educational setting.

A knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation.

SLC26A4 gene mutations lead to Pendred syndrome and non-syndromic hearing loss (DFNB4). The mouse model is well used to study the pathology of Pendred syndrome, however, mice with different Slc26a4 mutations exhibit different phenotypes, and these mice have severe deafness and inner ear malformations that are not imitated less severely Human phenotype. In this study, we generated a knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation to mimic the most common mutation found in human. Some L236P mice were observed to have significant vestibular dysfunction including torticollis and circling, the giant otoconia and destruction of the otoconial membrane was observed in L236P mice. Unlike other profoundly deafness in Slc26a4 mouse model, L236P mice present mild to profound hearing loss, consistent with the hearing threshold, inner ear hair cells also lost from slight to significant. Together, these data demonstrate that the L236P mouse phenotype is more similar to the human phenotype and should be used as a tool for further research into the human Pendred syndrome.

Changes in Swallowing Symptoms and Esophageal Motility After Thyroid Surgery: A Prospective Cohort Study.

INTRODUCTION: Swallowing difficulties, the pathophysiology behind which is incompletely understood, have been reported in 47-83% of goiter patients referred for thyroidectomy. We aimed at examining the influence of thyroid surgery on swallowing symptoms and esophageal motility. METHODS: Thirty-three patients with benign nodular goiter undergoing thyroid surgery were included. All completed high-resolution esophageal manometry examinations and the goiter symptom scale score, assessed by the thyroid-specific patient-reported outcome measure. The evaluations were performed before and 6 months after surgery. RESULTS: Before surgery, the goiter symptom score was median 39 points (range 2-61), which improved to median five points (range 1-52) after surgery (p < 0.001). The motility parameters were within the limits of normal swallowing physiology, both before and after surgery. Only the upper esophageal sphincter (UES) pressure increased significantly from 70.6 ± 27.7 to 87.7 ± 43.2 mmHg after surgery (p = 0.04). Using regression analyses, there was no significant correlation between change in goiter symptoms and weight of the removed goiter, motility parameters, or motility disturbances. However, patients undergoing total thyroidectomy experienced a larger reduction in pressure in the area of the UES and former thyroid gland after surgery in comparison with patients undergoing less extensive surgery. CONCLUSIONS: Goiter symptoms improved significantly after thyroidectomy, but without correlation to esophageal motility disturbances. This information is essential when interpreting dysphagia in patients with nodular goiter, and when balancing patients' expectations to surgical goiter therapy. REGISTRATION NUMBER: NCT03100357 ( www.clinicaltrials.org ).

Effectiveness and Mechanism of Preoperative Lugol Solution for Reducing Thyroid Blood Flow in Patients with Euthyroid Graves' Disease.

BACKGROUND: To reduce intraoperative and postoperative complications, using Lugol solution to preoperatively prepare patients with Graves' disease has (1) rapidly reduced the severity of thyrotoxicosis and (2) reduced the vascularity of the thyroid gland. The vascularity reduction normally accompanies reducing the severity of thyrotoxicosis. However, the effects and mechanism of Lugol solution for reducing blood flow have not been well investigated in the patients with euthyroid (normally functioning thyroid) Graves' disease. METHODS: Twenty-five patients with euthyroid Graves' disease being preoperatively treated with Lugol solution for 10 days were measured, at baseline and on the operative day, for (1) superior thyroid artery blood flow; (2) systemic angiogenic factor (VEGF); and (3) systemic inflammatory factor [interleukin (IL)-16]. RESULTS: All three parameters were significantly (p < 0.0001) lower after 10 days of Lugol solution treatment. The average reductions were blood flow: 60% (0.294 vs. 0.117 L/min), serum VEGF: 55% (169.8 vs. 76.7 pg/mL), and serum IL-16: 50% (427.2 vs. 214.2; pg/mL). CONCLUSION: Lugol solution significantly reduced thyroid arterial blood flow, VEGF, and IL-16, even in patients with euthyroid Graves' disease. We recommend routine preoperative Lugol solution treatment for all patients with Graves' disease.

[The clinical definition and etiology of Pendred syndrome (a review of the literature and clinical observations)]. / Sindrom Pendreda (obzor literatury i klinicheskie nablyudeniya).

The aim of this work was a clinical study of the patients with mutations in the SLC26A4 gene and clinical diagnosis of the Pendred syndrome. The Pendred syndrome is a hereditary autosomal recessive disorder characterized by combined pathology of the inner ear and the thyroid gland. CT of the temporal bones demonstrates the Mondini-type structural anomaly in the inner ear and enlarged vestibular aqueduct. Examination of the thyroid gland reveals hypothyroidism and euthyroid goiter. A total of 20 unrelated children at the age from 2 to 16 years presenting with the hearing loss of different severity were available for the examination. High-resolution CT of the temporal bones demonstrated abnormal development of the inner ear including the Mondini-type structural anomaly and enlarged vestibular aqueduct. Five children with congenital hypothyroidism suffered from bilateral sensorineural impairment of hearing. The routine methods of audiological and molecular genetic examination were used throughout the study. RESULTS: As a result of molecular genetic studies, four out of the 20 patients were found to carry six recessive mutations of the SLC26A4 gene in the compound heterozygous and one such gene in the homozygous state which confirmed the hereditary nature of the disease. The children suffered the hearing loss of varying severity diagnosed at different age. The thyroid hypofunction in one child was identified when it was 2 years of age, and in two children at the age of 8 and 9 years. CONCLUSION: The first step in the diagnosis of the Pendred syndrome among children with congenital hearing loss was a CT scan of the temporal bones that showed incomplete separation of the curls of the cochlea and enlarged vestibular aqueduct. It is necessary to continue to study epidemiology, clinical and molecular genetics of the Pendred syndrome in the Russian population.

Thymosin beta 10 correlates with lymph node metastases of papillary thyroid carcinoma.

BACKGROUND: Thymosin beta 10 (TMSB10) has recently been recognized as being an important player in the metastatic cascade including tumor angiogenesis, invasion, and metastasis. However, a role for this protein in papillary thyroid carcinoma (PTC) has not yet been established. METHODS: Real-time polymerase chain reaction was used to examine the expression of TMSB10 messenger RNA in 36 cases of thyroid tissue samples: normal thyroid, PTC without lymph node metastases (LNM) and PTC with LNM (n = 12 cases in each subgroup). For immunohistochemistry, 130 patients with PTC were selected during the period of 2004-2005, 91 with and 39 without LNM. Statistical analysis was applied to evaluate the correlation between TMSB10 expression and LNM of PTC. RESULTS: By real-time polymerase chain reaction analysis, the expression of TMSB10 messenger RNA in normal thyroid tissue, PTC without LNM, and PTC with LNM tissue were significantly different (P < 0.0001). On immunohistochemistry analysis of 130 patients with PTC, in which 91 cases had cervical LNM and 69 cases had central neck LNM, high expression levels for TMSB10 were more common in patients with cervical LNM compared with patients without (81% versus 33%, P < 0.001). Similarly, high expression levels of TMSB10 were more common in patients with central neck LNM compared with those without (87.0% versus 44.3%, P < 0.001). CONCLUSIONS: High expression levels of TMSB10 correlated with LNM in PTC, especially in the central neck region. Patients with PTC with low levels of TMSB10 expression may be unlikely to have central neck LNM and could therefore avoid prophylactic central neck dissection.

The Effect of Conventional Open Thyroidectomy on Clinical Results and Respiratory Function Tests in Multinodular Goitre.

AIM: The primary aim of our study was to measure the effect of conventional open thyroidectomy performed for patients with multinodular goiter (MNG) on pulmonary volumes measured with respiratory function tests independent from surgical indications. A secondary aim was to determine whether there was a significant improvement in the complaints due to obstructive symptoms after MNG surgeries. METHODS: This study was conducted between October 2020 and June 2022. Patients who were hospitalized to undergo surgery for giant multinodular goiter were prospectively included in the study. Patients were questioned about complaints of pressure, hoarseness, dyspnea, sleep apnea, snoring, and dysphagia before the surgery and during the follow-up 6 months after surgery. In addition, pulmonary function tests were performed preoperatively, 48 hours after surgery and 6 months after surgery. Forced expiratory volume in 0.5 seconds forced expiratory volume in 1 second and forced vital capacity values in pulmonary function test (PFT) measurements were recorded. RESULTS: A total of 55 patients, 42 females and 13 males, mean age 49.54 ± 13.6 years, were included in the study. Although there was a significant decrease in clinical symptoms caused by the thyroid volume within 6 months in patients who were operated for giant MNG there was no significant change in pulmonary function tests. There was a positive correlation between the thyroid volume and nodule weight in patients with MNG. CONCLUSIONS: Our results suggest that it is not necessary to follow up with patients without obstructive findings in preoperative pulmonary function tests with pulmonary function tests in the postoperative period.

Identification of two heterozygous deafness mutations in SLC26A4 (PDS) in a Chinese family with two siblings.

OBJECTIVE: To detect genetic cause of two Chinese siblings (patient 1 and 2) with Pendred syndrome. DESIGN: Patients and their parents underwent clinical and genetic evaluations. To identify genetic mutations, sequencing of SLC26A4 was carried out. STUDY SAMPLE: Two siblings and their parents. RESULTS: Clinical evaluations showed that patient 1 suffered from bilateral postlingual progressive sensorineural hearing loss with enlarged vestibular aqueduct and slight diffuse multinodular goiter with euthyroid, and patient 2 suffered from bilateral prelingual progressive sensorineural hearing loss with enlarged vestibular aqueduct and no goiter with euthyroid. Furthermore, the sequence analysis of SLC26A4 indicated that either of the two siblings presented a compound heterozygote for the c.919A>G mutation in the splice site of intron 7 and for the c.1548insC mutation in exon 14. Their mother was a heterozygous carrier of the splice site mutation in intron 7, and their father was a heterozygous carrier of the insertion mutation in exon 14. CONCLUSIONS: Mutation analysis identified a compound heterozygous mutation (c.919A>G/c.1548insC) in SLC26A4 in two Chinese siblings with Pendred syndrome. Also, c.1548insC was first reported in the Chinese population. Although the two siblings from the same family carried the same genotype, they presented different phenotypes.

Elevated serum IL-16 and RANTES levels in patients with autoimmune thyroid diseases and modulation by methimazole therapy.

Interleukine-16 (IL-16) and RANTES (regulated upon activation, normal T cell expressed and secreted) are 2 cytokines with the function of T helper cell recruitment, which might play a key role in pathogenesis of autoimmune thyroid diseases (AITD). This study was aimed to evaluate the IL-16 and RANTES in patients with AITD. Serum IL-16 and RANTES levels were measured in patients with Graves' disease (GD; n=45), Hashimoto's thyroiditis (HT; n=68), nontoxic multinodular goiter (NTMNG; n=20), and healthy individuals (n=61). The results showed that serum IL-16 and RANTES levels were elevated both in HT and higher in untreated GD patients when compared to NTMNG patients and the healthy individuals, which were decreased after MMI therapy in untreated GD patients. However, in HT patients, serum IL-16 and RANTES levels were comparable among the conditions of hyperthyroid and euthyroid received by l-thyroxine therapy and untreated hypothyroid. Furthermore, serum IL-16 levels were correlated with FT3, FT4, TRAb in GD, but not in HT patients. The data did not show any correlation between RANTES levels and clinical factors. In conclusion, IL-16 and RANTES might be involved in the pathogenesis of GD and HT, and serum IL-16 levels in GD maybe a potential marker of disease activity and severity.

Auditory-perceptual voice characteristics in pre-operative patients undergoing thyroid or parathyroid surgery.

OBJECTIVES: To systematically evaluate auditory perceptual voice characteristics in people with thyroid disease prior to undergoing thyroid surgery. PATIENTS AND METHODS: This study examined the auditory perceptual voice characteristics of 96 individuals with thyroid disease. Participants were categorised by type of thyroid disease (i.e. multinodular goitre, thyroid cancer, thyroid nodule, toxicity or parathyroidism) and by status of compression (i.e. compression versus no compression). Auditory perceptual voice ratings were made on samples of connected speech by using the Perceptual Voice Profile. RESULTS: A high prevalence of participants had deviant auditory perceptual voice features; however, the majority of these abnormalities were slight to mild in severity and only 8% of participants had a clinically significant auditory perceptual abnormality. There was no significant difference in features between diagnostic categories, and only high pitch was rated as more significantly deviant in patients without compression versus those with compression. CONCLUSIONS: This study supports the need for auditory-perceptual ratings to be included as part of pre-operative multidimensional assessment of voice in patients with thyroid disease.

[Peculiarities of formation, clinical presentations and therapy of diffuse nontoxic goiter of children].

The paper deals with the peculiarities of formation, clinical presentations and therapy of diffuse nontoxic goiter of children. The paper highlights the connection of the disease with the genetic predisposition, the impact of natural and anthropogenic strumagenes, immune processes. The clinical presentations of the diffuse nontoxic goiter are diffuse enlargement of thyroid gland, normal or high level of thyrotropichypophysis hormone when the content of thyroxin and triiodothyronine is normal, which is treated as the subclinic hypothyroidism syndrome. The variety of the disease pathogenesis theories leads to testing of different therapeutic methods, the principal ones among them are the use of iodine preparation and replacement therapy.

[Lazer-inducted interstitial thermotherapy in the treatment of solid nodulus of thyroid].

The results of treatment 272 patients with a nodular colloid goiter with the use of lazerinducted termotherapy (LITT) are analysed. I is established that in the developed modes of LITT application does not cause destructive changes in paranodular tissue and disorders of thyroid gland hormonal function. Duration of reverse development and substituting of nodular for a connecting tissue is determined by echogene and volume. With it increase the intensity of nodulus substituting for a connecting tissue goes down, extended the terms of nodulus regress. The indication to the repeated application of termotherapy is remaining tissue in the projections of nodulus scope from 42% and more an initial volume through 6 ms treatment. Absolute indications to repeated LITT is a presence of thyroid epithelium in remaining tissue of nodulus.

Absence of primary hypothyroidism and goiter in Slc26a4 (-/-) mice fed on a low iodine diet.

BACKGROUND: Mutations in the SLC26A4 gene, coding for the anion transporter pendrin, are responsible for Pendred syndrome, characterized by congenital sensorineural deafness and dyshormonogenic goiter. The physiological role of pendrin in the thyroid is still unclear and the lack of a thyroid phenotype in some patients with SLC26A4 mutations and in Slc26a4 (-/-) mice indicate the existence of environmental or individual modifiers able to compensate for pendrin inactivation in the thyroid. Since pendrin can transport iodide in vitro, variations in iodide supply have been claimed to account for the thyroid phenotype associated with pendrin defects. AIM: The Slc26a4 (-/-) mouse model was used to test the hypothesis that iodide supply may influence the penetrance and expressivity of SLC26A4 mutations. MATERIALS AND METHODS: Slc26a4 (-/-) and (+/+) mice were fed up to 6 months on a standard or low iodine diet and were evaluated for thyroid structural abnormalities or biochemical hypothyroidism. RESULTS: A 27-fold iodide restriction induced similar modifications in thyroid histology, but no differences in thyroid size, T4 or TSH levels were observed between between Slc26a4 (-/-) and (+/+) mice, either in standard conditions and during iodine restriction. CONCLUSIONS: Iodide restriction is not able to induce a thyroid phenotype in Slc26a4 (-/-) mice. These experimental data, together with those coming from a review of familial Pendred cases leaving in regions either with low or sufficient iodide supply, support the idea that the expression of thyroid phenotype in Pendred syndrome is more powerfully influenced by individual factors than by dietary iodide.

Post-ablative hypothyroidism.

OBJECTIVE: To determine the incidence of hypothyroidism following radioactive iodine (RAI) treatment for hyperthyroidism and to study the relationship between pretreatment RAI uptake and treatment dose and the subsequent development of hypothyroidism. METHODS: Retrospective chart review of patients treated with RAI for hyperthyroidism between 1995 and 2000. 180 charts were reviewed; 41 met the inclusion criteria. Data were collected regarding the cause of hyperthyroidism, initial RAI uptake, initial dose of RAI, number of RAI treatments, and post treatment thyroid status. RESULTS: Patients in toxic nodular goiter group had significantly lower 24-hour RAI-123 uptake as compared to those with Graves' disease. However patients with Graves' disease received significantly lower RAI dose in comparison to those with toxic nodular goiters. Cure rates following RAI administration were similar in both groups. 70% of patients with Graves' disease developed post-ablative hypothyroidism as compared to 42% in toxic nodular goiter group (p = 0.086). There was no relationship between the dose of RAI or pretreatment RAI uptake and the likelihood of developing hypothyroidism. CONCLUSION: We found that, within our study population, post-ablative hypothyroidism tended to be more prevalent in patients with Graves' disease as compared to those with toxic nodular goiter. However cure rates following RAI administration were similar in both groups. We also found that neither the magnitude of the administered RAI dose nor the pre-treatment RAI uptake predicted the development of subsequent hypothyroidism.

P-wave dispersion in endogenous and exogenous subclinical hyperthyroidism.

BACKGROUND: The aim of this study was to measure maximum P wave duration (Pmax) and P wave dispersion (PWD), which can be indicators for the risk of paroxysmal atrial fibrillation when increased, and to reveal their relationship with thyroid hormone levels in patients with endogenous and exogenous subclinical hyperthyroidism. METHODS: Seventy-one patients with sublinical thyrotoxicosis (34 endogenous, 37 exogenous) and 69 healthy individuals were enrolled in the study. Pmax and minimum P wave duration (Pmin) on electrocardiogram recordings were measured and PWD was calculated as Pmax-Pmin. RESULTS: Pmax (p<0.001) and PWD (p<0.001) values were significantly higher in patients with endogenous subclinical hyperthyroidism compared with the control group. Pmax (p<0.001) and PWD (p<0.001) values were significantly higher in patients with exogenous subclinical thyrotoxicosis compared with the control group. Pmax (p=0.710) and PWD (p=0.127) were not significantly different in patients with endogenous subclinical hyperthyroidism compared with exogenous subclinical hyperthyroid patients. Pmax and PWD negatively associated with TSH in endogenous and exogenous subclinical hyperthyroidism. CONCLUSION: In the present study, we observed that Pmax and PWD were longer in patients with endogenous and exogenous subclinical hyperthyroidism. Lack of a difference in Pmax and PWD between patients with endogenous and exogenous subclinical hyperthyroidism seems to support the idea that hormone levels rather than the etiology of thyrotoxicosis affect the heart.

The thyroid angiofollicular units, a biological model of functional and morphological integration.

The fundamental role of the thyroid gland is to ensure the biosynthesis of thyroid hormones whose primary role during embryonic development and the maintenance of homeostasis after birth is well known. The challenge here is double, as the hormone synthesis depends on both potentially toxic biochemical processes, as long as they are not fully contained, and the availability of a trace element, iodine, whose uptake may be extremely variable depending on the geographical location and the physiological status of individuals. The squaring of the circle has been resolved by the thyroid gland during its phylogenetic maturation by setting up angiofollicular units, morphological entities whose the perfect functional coherence between the different compartments within them (epithelial, endothelial and interstitial) results from a high level three-dimensional assemblage. This morphological and functional integration warrants adequate supplies of thyroid hormones whose mobilization must be triggered at any time when necessary. This functional requirement finds its expression in the morphological heterogeneity that ultimately culminates in the formation of nodules. Each angiofollicular unit is an individualized entity with its own genotypic and phenotypic asset that runs on the extrinsic control of TSH and a host of autocrine and paracrine factors. But subtle intrinsic mechanisms of self-regulation, operating out of any outside influences, constantly adjust the availability of players involved in the hormonal synthesis (iodine, thyroglobulin) within a biochemical entity (the thyroxisome) that is perfectly suited for this synthesis taking place without prejudice to the thyrocyte. The hormonal synthesis generates oxygen-derived substances as oxidative load or stress, though perfectly controlled in healthy thyrocytes. Any injury related to the nature, the amount, or where in the cell oxygen-derived substances are produced, may lead to morphological and functional breakdowns responsible for various disease processes, including those of autoimmune or even neoplastic nature.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects.

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-ß had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-ß going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-ß no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

Thyroid gland changes in patients with acromegaly.

OBJECTIVE: Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. SUBJECTS AND METHODS: In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. RESULTS: Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. CONCLUSIONS: Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75.